Autotransporters are a unique class of proteins found in bacteria, particularly Gram-negative species. These proteins play a fundamental role in how bacteria interact with their environment, including host organisms. They are distinguished by their inherent ability to facilitate their own transport across the bacterial outer membrane. This self-sufficiency in secretion allows bacteria to deploy various functions to their exterior, influencing their survival and interactions.
What Are Bacterial Autotransporters?
Bacterial autotransporters represent a large family of virulence proteins predominantly found in Gram-negative bacteria. They are unique because they can transport themselves across the bacterial outer membrane without requiring additional complex machinery.
These proteins are generally composed of two primary functional parts. The N-terminal “passenger” domain is the part that extends outside the cell and carries out the protein’s specific function. The C-terminal “beta-barrel” domain, on the other hand, is embedded within the outer membrane and acts as the channel for the passenger domain’s secretion.
The Self-Secretion Mechanism
The journey of an autotransporter begins with its synthesis in the bacterial cytoplasm, where it includes an N-terminal signal peptide. This signal peptide directs the nascent protein to the Sec translocase system, which facilitates its movement across the inner bacterial membrane into the periplasm.
Once in the periplasm, the signal peptide is cleaved off, releasing the autotransporter into this space. Within the periplasm, chaperone proteins help keep the autotransporter in an unfolded state, preventing premature folding before it reaches its destination. The C-terminal beta-barrel domain then inserts into the outer membrane, forming a pore.
The passenger domain subsequently translocates through this newly formed pore to the cell surface. This process often involves the passenger domain threading through the barrel in an unfolded or partially folded conformation. After reaching the cell surface, the passenger domain may either remain attached to the outer membrane or be cleaved and released into the extracellular environment, depending on the specific autotransporter and its function.
Diverse Functions of Autotransporters
Autotransporters perform a wide array of functions for bacteria, many of which are directly involved in their ability to cause disease.
One common function is adhesion, where autotransporters help bacteria stick to host cells or surfaces, which is an initial step in many infections. Examples include adhesins found in Escherichia coli and pertactin in Bordetella pertussis, which aid in bacterial attachment. Some autotransporters act as proteases, enzymes that break down host proteins, such as the IgA protease in Neisseria species, which cleaves antibodies to help bacteria evade the immune system.
Beyond proteolysis, autotransporters can contribute to immune evasion through various mechanisms, including binding to host complement-regulatory factors or modulating immune cell signaling. Certain autotransporters can also function as toxins or facilitate the delivery of toxic components to host cells, contributing to cytotoxicity. Other enzymatic activities, like lipase or sialidase functions, also promote bacterial survival and colonization in different environments.
Autotransporters as Targets for Medical Intervention
The exposure of autotransporters on the bacterial cell surface and their involvement in virulence make them attractive targets for developing new medical interventions. Strategies targeting these proteins could offer novel ways to combat bacterial infections, especially in an era of increasing antibiotic resistance.
One promising area is vaccine development, where autotransporter proteins or parts of them can be used as antigens to stimulate a protective immune response. For instance, pertactin from Bordetella pertussis is a component of some human vaccines against whooping cough. Research also explores using autotransporters to display other antigens, potentially leading to multivalent recombinant vaccines.
Another avenue involves developing antimicrobial strategies that inhibit autotransporter function or secretion. Such anti-virulence drugs aim to disarm pathogenic bacteria rather than outright kill them, which could reduce the selective pressure for antibiotic resistance. By interfering with processes like adhesion or toxin delivery, these drugs could make bacteria less harmful and more susceptible to the host’s immune system.